We are analyzing the pathogenesis of a number of selected neurological and neuromuscular mutants in mice with the hope that they may clarify mechanisms of human hereditary neuromuscular diseases. The overall goals of these studies are to achieve an understanding of the primary gene effect(s) and underlying mechanisms leading to each of the mutant syndromes. Mutations under investigation are qk (quaking), jp (jimpy), and its allele jpmsd (myelin synthesis deficiency) representing disorders of myelin metabolism and also several more recently discovered neurological mutations whose defects are as yet totally unknown. Mutant mice suffering from abnormal locomotion or posture without anatomical lesions are being screened for involvements of catecholaminergic mechanisms. They are rabbit (rb), hotfoot (ht), jolting (jo), Nm 133, and nm 206 (both as yet unnamed).